Kazuyo Kegan, PhD

Anesthesiology and Critical Care ManagementJohns Hopkins University School of MedicineTitle: "Hypoxia-inducible factor-1 mediates Th2 immune response during development of pulmonary hypertension"Term: October 1, 2011 and will end September 30, 2013

Summary of Research Project:

Injury to endothelium may be a trigger of pulmonary vascular remodeling in pulmonary hypertension (PH). When the pulmonary endothelium becomes damaged, wound repair cascades are stimulated. Recently, bone marrow-derived cells and circulating immune cells have been suggested to be recruited to the site of remodeling vascular wall, as well as lung resident cells, for this repair process. Failure to stop the initial repair response could result in pathophysiological vascular remodeling. T lymphocytes that express CD4 are also known as T helper (Th) cells; they are regarded as the most prolific producers of cytokines. We have previously shown that Th2 cytokine IL-4 is critical to the initiation of proliferating activity in the pulmonary vasculature and development of PH. In this proposal, we will dissect the mechanism by which the Th2 response triggers endothelial injury and recruitment of bone marrow and immune cells to the site of remodeling vasculature during the development of PH. The purpose of this proposal is to provide a better guide for the therapies that are based on the central role of endothelial injury and circulating cell recruitment caused by innate immune response.

Curriculum Vitae

NAME: Kazuyo Kegan, PhDPOSITION TITLE: Research Associate

EDUCATION/TRAINING

INSTITUTION AND LOCATION

DEGREE

YEAR(S)

FIELD OF STUDY

Kagoshima University Dept of Agriculture, Kagoshima, JapanKagoshima University School of Medicine, Laboratory and Vascular Medicine, Japan

BA

1995

BiochemistryMolecular Cell Biology and Hematology

The United Graduate school of Agricultural Sciences, Kagoshima University, Kagoshima, Japan

2010 The J Immunology article (#15, PMID: 20889544) was featured in the Journal of Immunology's editorial topic that highlights articles that are among the top 10% of articles published in the journal.

2010 The J Immunology article (#15, PMID: 20889544) was featured by the Faculty of 1000 Biology (F1000) and noted as one of the top 2% of all papers published.

Selected Peer-reviewed Publications

Maruyama I, Nakata M, Yamaji K. Effect of leptin in platelet and endothelial cells; Obesity and arterial thrombosis. Annals of the New York Academy of Sciences 902:315-319 (2000). PMID: 10865855

Research Support

Ongoing Research Support

NIH NHLBI, Paul M. Hassoun, MD 01/01/07-12/31/2011 SCCOR 5P01HL058064-119001 "Molecular Determinants of Pulmonary Arterial Hypertension" Project 4: Hypoxia-Induced Mitogenic Factor (FIZZ1) in Pulmonary Hypertension and Right Heart Failure Principal Investigator: Roger A. Johns, MD, MHS Aims: 1) Examine the role of HIMF/FIZZ1 in the mechanism of pulmonary hypertension using genomic and proteomic analysis in animal models 2) Use genomic, proteomic, and physiologic/pharmacologic approaches to examine HIMF effect on components of known downstream HIMF signaling pathways. 3) Identify the HIMF receptor(s) and/or binding partners in lung and heart utilizing proteomics to identify its interactome network and post-translational modifications. 4) Investigate the role and mechanism of HIMF inhibition in the protective and reversal actions of simvastatin and sildenafil on remodeling in of PAH.

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